ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.4986+5G>C

dbSNP: rs397509211
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000258270 SCV000326084 pathogenic Breast-ovarian cancer, familial, susceptibility to, 1 2015-10-02 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV002519025 SCV003442377 likely pathogenic Hereditary breast ovarian cancer syndrome 2022-08-21 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 267562). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the c.4986+5G nucleotide in the BRCA1 gene. Other variant(s) that disrupt this nucleotide have been determined to be pathogenic (PMID: 23239986, 23451180, 30209399). This suggests that this nucleotide is clinically significant, and that variants that disrupt this position are likely to be disease-causing. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. Experimental studies have shown that this variant affects BRCA1 function (PMID: 30209399). This variant has been observed in individual(s) with breast and/or ovarian cancer (PMID: 27062684). This variant is not present in population databases (gnomAD no frequency). This sequence change falls in intron 15 of the BRCA1 gene. It does not directly change the encoded amino acid sequence of the BRCA1 protein. It affects a nucleotide within the consensus splice site.
Myriad Genetics, Inc. RCV000258270 SCV005083825 likely pathogenic Breast-ovarian cancer, familial, susceptibility to, 1 2024-05-21 criteria provided, single submitter clinical testing This variant is considered likely pathogenic. This variant is strongly associated with more severe personal and family histories of cancer, typical for individuals with pathogenic variants in this gene [PMID: 25085752].
Brotman Baty Institute, University of Washington RCV000258270 SCV001243878 not provided Breast-ovarian cancer, familial, susceptibility to, 1 no assertion provided in vitro

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.